Water plays a vital role in the proper functioning of earth ecosystem and also essential for fish life. In autumn season, 2016, three different regions from El-Manzla Lake (El-Boughaz, Domiette and El-Ganka) were selected to determine their water quality and bacterial contaminations. Water, sediment and fish samples were collected from four different sites of each region. The selected regions are exposing to direct and indirect industrial, municipal wastewater and agricultural drainage disposals. The results showed that El-Ganka region had significantly (P<0.05) highest nitrogenous compounds (NH3-N, NO2 & NO3), total nitrogen, total and available phosphorus and Chlorophyll a followed by Domiette and then El-Boughaz. While had the significantly (P<0.05) lowest pH and secchi disk (SD). Water exchange between the Mediterranean Sea and the lake led to significant increase values (P<0.05) in its salinity and conductivity at the El-Boughaz region. Also, some bacteriological characteristics (Bacterial count, coliform and some pathogens) in water, sediment and some fish organs (skin, muscle & gills) of Oreochromis niloticus and Clarias gariepinus were determined.  Total bacterial count, coliform group, fecal coliform and Vibrio cholera recoded higher values in sediment than in water. Total bacterial count and coliform group in the muscle of the two investigated fish species had lower values than skin and gills, while fecal coliform and vibrio were not detected. Gills recorded higher values than those in the skin. Muscles of Clarias gariepinus recorded higher levels in all bacterial parameters than the Oreochromis niloticus in contrast the skin and gills. On base of the present study, it could be concluded that Manzala' lake water resources need more attention to be protected for aquaculture purposes and sustainable development through the detection of aquatic biological agents and possible control of water quality.